Blood coagulation ultimately depends on the thrombin-catalysed conversion of Fibrinogen to fibrin. Diminished or nondetectable levels in fibrinogen (hypo- and afibrinogenemia) and functionally impaired fibrinogen (dysfibrinogenemia) have been described in patients with varying degree of severity in hemorrhagic manifestations. We propose to use recombinant DNA techniques to clone and characterize the genes coding for the three polypeptides of fibrinogen and to compare and study the organization of their structural and regulatory elements. We further propose to extend these studies to elucidate the nature of the genetic changes that have occurred in patients with congenital fibrinogen defects and correlate these changes with the dysfunctions which ensue. The successful cloning and characterization of the human fibrinogen genes will, eventually, permit us to develop molecular probes to study the evolution of the fibrinogen genes and their control.